New preprint out from the lab today, led by @alvalesano. A little thread. 1/x

SARS-CoV-2 Genomic Surveillance Reveals Little Spread Between a Large University Campus and the Surrounding Community medrxiv.org/content/10.110…
You may remember way back in Fall 2020, there was a lot of talk about college towns and how outbreaks on campuses related to case counts in the surrounding communities. For example, article below. 2/x
nytimes.com/2020/09/06/us/…
If you live in a college town like me, this has been an ongoing topic of conversation. We decided to take a look at this. Thanks to @dho @tcfriedrich who got us interested in this question. 3/x
Crux of the question is whether viruses flow from students to the surrounding community, thereby causing sequential spikes in cases - campus outbreak followed by community surge. Genomic epidemiology can shed light on this question. 4/x
University of Michigan is a large institution in Washtenaw County. We also have a major academic medical center. We started prospective large-scale surveillance in late August, collecting all positive samples tested at our hospital micro lab and University Health Services. 5/x
We didn't capture every case of course. People on campus and in the community got tested outside of our system. Our sampling was pretty awesome though. ~20% cases in students and also ~25% of cases in the County or ~5% of cases in Michigan Region 2S. 6/x
Here's the overall case curves with students in green. Then there was a big case surge in November locally and across Michigan. 7/x
Let's look at the genomes! We sequenced 1659 viruses total, 468 from students, 1191 from non-students. On this tree, students have red tips. There were ~200 viral introductions to the student population. Two were large clusters, 115 and 73 students. 171 were singletons. 8/x
These clusters weren't located to a specific residence hall - or one super spreading event. They crossed multiple halls and also to students off campus. Did they spread to the community? 9/x
Not really! These two clusters were pretty much their own PANGO lineages, B.1.1.304 and B.1.593. They have rarely been seen outside of Michigan or even outside our study. As shown here (blue and yellow). They are largely absent in the subsequent November surge (grey). 10/x
We also did a formal analysis of how many "community" genomes were descended from "student" nodes. Out of 1191 genomes from non-students, 96% were NOT descended from students. 11/x
Of those 53 descendants, most (18 and 11) were nested within those two large clusters. 12/x
So, in a well-sampled population we find little evidence that viruses from students caused significant cases in the surrounding community. Lots of viruses came in during the Fall and circulated, but there wasn't a lot of movement of viruses to the community. 13/x
This is contrary to what has been a common narrative in college towns. Of course, there are some limitations here - and nuance. Please read the discussion. We didn't sample every case and this isn't contact tracing, so we aren't saying that there wasn't campus->community 14/x
And we don't have individual level data to delineate points of contact between students and the community.

But our sampling is good enough to say that student outbreaks were likely not a big driver of the subsequent surge of cases. 15/x
Feedback welcome!

Thanks to @alvalesano @itswillfitz @LaserInUse64 @The_Woods_Lab @MartinEpi @jgpetrie @tcfriedrich @dho, our UHS colleagues, Julie Gilbert.

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More from @LauringLab

18 Mar
Teaching virus evolution to grad students tomorrow. Just reread the assigned paper. I think it's relevant to the discussion on immunocompromised hosts and VOC. Like most things COVID, we forget lessons from other viruses 1/x
journals.plos.org/plospathogens/…
Those who know me know that I love geeking out on within-host evolution and I love geeking out on poliovirus. So I will try to hold myself in check. Briefly, oral poliovirus OPV is live attenuated virus vaccine, so it replicates in gut and shed in stool. Thus, it evolves. 2/x
See recent work from @alvalesano @mt2fus @famulare_mike and others on this. It's long been recognized that individuals with primary immunodeficiencies related to antibody generation can have prolonged "infections" with OPV. 3/x
cell.com/cell-host-micr…
Read 11 tweets
16 Mar
Seeing lots of analyses scraping GISAID data and looking at variant sequences / total sequences. I've heard chatter in my corner of the world that "Wow, Michigan really has a variant problem." Do we? Short thread about putting the epidemiology back in genomic epidemiology 1/x
In Michigan, who uploads sequence data? Vast majority comes from our awesome State Lab and then my lab. Since 1/1, my lab has uploaded 1146 to GISAID. Don't know State Lab numbers but at least 2x that. There are 600+ B.1.1.7 from Michigan, according to CDC 2/x
Why is that important? Well you need to know how sequencing is done. My lab is sequencing broadly in our area - we do every positive that we can get our hands on. We've been getting sequences uploaded on > 25% of cases since September. We've done better since January. 3/x
Read 12 tweets
20 Jan
Happy to share out latest preprint on SARS-CoV-2 within host diversity. Brief thread.
biorxiv.org/content/10.110…
We've been interested in within-host diversity for some time. It's important for understanding how mutations accumulate over time (relevant for how variants arise). Important for understanding how likely it is for variants to transmit and potentially for inferring trx chains 2/x
We looked at inpatients and outpatients. First we measured viral load. Why? Cause we're interested. But it's also a big factor in looking at diversity within hosts (spoiler alert). Another important (unique?) thing in our study is we analyzed data by day from symptom onset 3/x
Read 11 tweets
29 Dec 20
Unfortunately very few - any? - studies that I’ve seen relating viral load to outcome stratify by day post infection or symptom onset. This is big issue (viral load varies by day and people vary in when they get tested in disease course for many reasons). nytimes.com/live/2020/12/2…
For example, here’s data from my lab showing viral load by day for outpatients (purple) vs hospitalized patients (green). All tests were on presentation. If you just look at viral load on presentation, outpatients were higher - they were just tested earlier.
H/t to @Kalee_Rumfelt in my lab who did the chart review. Most studies don’t have day post symptom onset because it’s hard to retrieve. You typically don’t get it in data pulls from EMR. You have to go into chart notes one by one.
Read 4 tweets
24 Dec 20
Been thinking more about this piece from @kakape this morning and have some thoughts to share. So thought I'd do a Xmas eve thread about SARS-CoV-2/COVID19 and immunocompromised hosts. (1/x)
sciencemag.org/news/2020/12/u…
I emphasize that I respect the stated opinions out there and don't have doubts about data or what they may show. Just feel there's a perspective missing from the conversation. What can I bring to conversation? I am an infectious disease physician and study virus evolution. (2/x)
I have taken care of patients with COVID19 who have a range of immunocompromising conditions. I have also published on within host evolutionary dynamics of viruses. We published a preprint in Sept and subsequent JID paper on long term evolution in lymphoma patient. (3/x)
Read 20 tweets
20 Dec 20
With the news of this new variant and discussions of what it means for vaccines, keep thinking about this article from @SCOTTeHENSLEY and Yewdell (who very much needs a Twitter account). Short thread.

science.sciencemag.org/content/326/59…
First question from ID docs and many virologists I know is “OMG, what does this mean for vaccines.” We grow up in this pathogen vs. immune system paradigm that is sometimes distracting from issues at play. (2)
Many variants have been reported to escape this serum or that monoclonal. But large scale selection of a variant at this point is probably not driven by immune system (just not that much immunity around). (3)
Read 10 tweets

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